1. Field of the Invention
This invention relates to a physiologically balanced, ionized, acidic solution that is useful in wound healing and other applications in which antimicrobial properties are desirable. Preferably, the ionized solution is prepared by electrolysis, i.e. it is an electrolyzed solution. In addition, the invention relates to a methodology of using the solution of the invention, including a specialized bandage which may be used in combination with the solution or with other solutions or topically applied materials.
2. Brief Description of the Background Art
Various electrolyzed acidic salt solutions, their properties, and their uses have been described in the art. Several examples are provided below.
U.S. Pat. No. 5,622,848, issued Apr. 22, 1997, to Morrow, discloses a microbicidal solution for in vivo and in vitro treatment of microbial infections. The solution comprises an electrolyzed saline containing regulated amounts of ozone and active chlorine species, wherein the ozone content is between about 5 and 100 mg/L, and the active chlorine species content is between about 5 and 300 ppm. The active chlorine species comprises free chlorine, hypochlorous acid, and the hypochlorite ion, as measured by a chlorine selective electrode. The solution is prepared by subjecting a 1% or less saline solution to electrolysis under conditions sufficient to produce the desired active ingredients. The solution is preferably utilized at an isotonic saline concentration, and may be adjusted with hypertonic saline. The solution may be used for in vitro treatment of infected whole blood, blood cells, or plasma to reduce contamination, and may be used in the treatment of fluids infected with HIV, hepatitis, and other viral, bacterial, and fungal agents. The solution may also be administered to warm-blooded animals, including humans, by intravenous injection or other modes, for similar purposes.
PCT publication No. WO9934652, published Jul. 8, 1999, of Marais, discloses the use of an electrochemically activated sodium hypochlorite-free irrigating medium to reduce the proliferation of bacteria and other microorganisms during tooth root canal. Anion-and cation-containing solutions are obtained by electrolysis of a 10% aqueous NaCl solution. The anion-containing solution is used at a pH of about 2-7 and an oxidation reduction potential (ORP) of about +1170 mV; the cation-containing solution is used at a pH of about 7-13 and an ORP of about xe2x88x92980 mV.
X. W. Li et al. (Chinese J. Epidem., 17(2), pp. 95-98, 1996) reported a preliminary study of the microbicidal effect of electrolyzed oxidizing water. Electrolyzed oxidizing water was shown to completely kill Staphylococcus aureus and Escherichia coli within 15 seconds, while 10 minutes were required to completely kill all spores of Bacillus subtilus var. niger. Thirty seconds were needed to destroy the antigenicity of HBsAg. The oxidation reduction potential and pH values of electrolyzed oxidizing water were not significantly changed when stored for three weeks at room temperature under air-tight, light-free conditions.
A. Iwasawa et al. (J. Jap. Assoc. Infec. Diseases, 70(9), pp. 915-922, 1996) evaluated the bactericidal effect of acidic electrolyzed water on S. aureus, S. epidermidis, and Pseudomonas aeruginosa. At pH 5.0 to approximately 6.0, three bacterial strains were killed soon after being exposed to the acidic water containing 50 mg/L chloride, and the chloride concentration reportedly did not change after standing open for 6 hours. At pH 2.67 to approximately 2.80, the bactericidal effects were observed at a chloride concentration of 5 mg/L, and 80% of the chloride reportedly remained after standing open for 6 hours.
H. Tanaka et al. (J. Hosp. Infect., 34(1), pp. 43-49, 1996) reported on the antimicrobial activity of superoxidized water. Superoxdized water is described as xe2x80x9ca strong acidic and colorless solution with a high oxidation-reduction potential. The solution is prepared by mixing a small amount of salt with tap water in an electrolyserxe2x80x9d. The antimicrobial activity of superoxidized water was tested against methicillin-sensitive S. aureus, Serratia marcescens, E. coli, P. aeruginosa, and Burkholderia cepacia. The number of bacteria was reduced below the detection limit following incubation in superoxidized water for 10 seconds. The bactericidal activity of superoxidized water was similar to that of 80% ethanol, but superior to that of 0.1% chlorhexidine and 0.02% povidone iodine.
Y. Inoue et al. (Artificial Organs, 21(1), pp. 28-31, 1997) reported on the use of electrolyzed strong acid aqueous solution lavage in the treatment of peritonitis and intraperitoneal abscess. Peritoneal and abscess ravages were performed using an electrolyzed strong acid aqueous solution to treat seven patients with peritonitis and intraperitoneal abscesses. The period of irrigation in the seven patients ranged from 9 to 12 days, with conversion to microorganism negative state observed within 3 to 7 days. The authors describe the solution as being xe2x80x9cacidic water that contains active oxygen and active chlorine and possesses a redox potentialxe2x80x9d
S. Sekiya et al. (Artificial Organs. 21(1), pp. 32-38, 1997) reported on the use of electrolyzed strong acid solutions in the treatment of infectious skin defects and ulcers using. The clinically applied therapy of electrolyzed strong acid aqueous solutions were found to be effective in the treatment of infectious ulcers. Sekiya et al. describe the strong aqueous solution (ESAAS) as being xe2x80x9cgenerated by electrolyzing water and a small quantity of salt with a cation transfer filter.xe2x80x9d
H. Hayashi et al. (Artificial Organs, 21(1), pp. 39-42, 1997) reported on the use of electrolyzed strong acid aqueous solutions (ESAAS) in the treatment of mediastinitis following cardiovascular surgery. Hayashi et al. described ESAAS as being xe2x80x9cproduced by electrolyzing sodium chloride solution. ( . . . ) ESAAS is produced by electrolyzing the sodium chloride solution using an ion-exchange membrane that separates the positive and negative electrodes. A small amount of sodium chloride is added to the water to facilitate electrolysis and increase the concentration of dissolved chloride.xe2x80x9d The mediastinal wound was left open and irrigated with ESAAS one to three times daily until the infection was eradicated. Satisfactory growth of granulation tissue was observed in all patients treated, with no evidence of adverse effects attributable to ESAAS.
N. Tanaka et al. (Artificial Organs, 23(4), pp. 303-309, April 1999) reported on the use of electrolyzed strong acid aqueous solutions to clean and disinfect hemodialysis equipment. The solutions were found to directly inactivate bacterial endotoxins, and proved to be more economical than the conventional disinfecting method. The xe2x80x9celectrolyzed strong acid aqueous solutions are disclosed to be xe2x80x9cstrongly acidic water which is made by electrolyzing tap water containing 50-1000 ppm salt (NaCl  greater than 99% pure) in a cell partitioned by a polyester diaphragm. It has an acidity of 2.3-2.7 pH, more than 1,000 mV in oxidation-reduction potential and 10-50 ppm in available: chlorine.xe2x80x9d
J. B. Selkon et al. (J. Hosp. Infec., 41(1), pp. 59-70, January 1999) evaluated the antimicrobial activity of a new superoxidized water, STERILOX(copyright) (Sterilox Medical Limited, 85 E Milton Park, Abingdon, Oxon OX14 4RY, UK) for the disinfection of endoscopes. This superoxidized water is described as being xe2x80x9cgenerated at the point of use by passing a saline-solution over coated titanium electrodes at 9 amps. The product generated has a pH of 5.0-6.5 and an oxidation reduction potential of  greater than 950 mV.xe2x80x9d The antimicrobial activity of STERILOX(copyright) was tested against Mycobacterium tuberculosis, M. avium-intracellulare, M. chelonae, E. coli (including type 0157), Enterococcus faecalis, P. aeruginosa, B. subtilus var. niger spores, methicillin-resistant S. aureus, Candida albicans, poliovirus type 2, and human immunodeficiency virus HIV-1. Under clean conditions, freshly generated STERILOX(copyright) was found to be highly active against all these microorganisms, giving a 5 log, (99.999%) or greater reduction in 2 minutes or less.
K. S. Venkitanarayanan et al. (Appl. and Env. Microbiol., 65(9), pp. 4276-4279, September 1999) evaluated the efficacy of electrolyzed oxidizing water for inactivating E. coli O157:H7, Salmonella enteritidis, and Listeria monocytogenes. A five-strain mixture of E. coli O157:H7, S. enteritidis, or L. monocytogenes was inoculated in electrolyzed oxidizing water at various temperatures, for various time periods. The electrolyzed oxidizing water is produced from a saline base solution containing approximately 12% by weight NaCl. At 4xc2x0 C. and 23xc2x0 C., an exposure time of 5 minutes, the population of all three pathogens in the treatment samples was reported to be reduced by approximately 7 log CFU/mL, with compete inactivation by 10 minutes of exposure. A reduction of greater than 7 log CFU/mL in the levels of the three pathogens was reported to occur in the treatment samples incubated for 1 minute at 45xc2x0 C. or for 2 minutes at 35xc2x0 C.
This invention relates to physiologically balanced, ionized, acidic solutions and to 11 a methodology for their use, including a specialized bandage which may be used in combination with the solutions, or with other topically applied materials. Preferably the ionized solutions are prepared by electrolysis, i.e. they are electrolyzed solutions.
The composition of the invention is prepared using a mixture of inorganic salts in physiologically balanced proportions. A mixture of inorganic salts and, optionally minerals, (such as metallic elements, for example and not by way of limitation) is used in order to mimic the electrolyte concentration and mixture of body fluid in an isotonic state. The solution typically comprises halide salts of sodium, potassium, calcium, and other cations. Typically the halide is fluoride, chloride, bromide, or iodide, and most typically chloride. The concentrations of these salts in combination with particular minerals are such that they give the electrolyzed composition its unique properties.
In accordance with the present invention, we have created a composition comprising a physiologically balanced, electrolyzed acidic solution, where the starting solution prior to electrolysis comprises a total concentration of halide-comprising salts ranging from about 0.4 g/L to about 16 g/L; more preferably ranging from about 4 g/L to about 12 g/L; and, most preferably, ranging from about 5.2 g/L to about 6.2 g/L. The solution may optionally contain other salts or minerals. The electrolyzed solution has a pH within the range of about 2 to about 6, an oxidation reduction potential within the range of about +600 mV to about +1200 mV, and a titratable halide (X) content within the range of about 10 ppm to about 100 ppm, where X is Fxe2x88x92, Clxe2x88x92, Brxe2x88x92, or Ixe2x88x92.
The starting solution used to prepare the physiologically balanced, electrolyzed, acidic composition of the invention preferably comprises a plurality of halide-comprising salts selected from the group consisting of sodium halide, potassium halide, magnesium halide, calcium halide, zinc halide.
The starting solution of halide-comprising salts, and optionally-other salts and minerals, is converted to acidic water through electrolysis. The electrolyzed, halide-comprising solution has a typical oxidation reduction potential (ORP) of about +600 to +1200 mV. The pH of the electrolyzed, chlorine-comprising solution is typically lowered to about 6 or less, giving the solution bactericidal, fungicidal, and sporicidal properties. The halide-comprising acidic solution is physiologically balanced by the inclusion of elements such as sodium, potassium, magnesium, zinc, lithium, and beryllium in the solution. Typically these elements are supplied in the form of halide-comprising salts which are ionized during electrolysis. Preferably, these physiologically-balancing halide-comprising salts are selected from the group consisting of sodium halide, potassium halide, magnesium halide, zinc halide, lithium halide, beryllium halide, and combinations thereof. Most preferably the salts are selected from sodium chloride, potassium chloride, magnesium chloride, zinc chloride, and combinations thereof.
A particularly preferred starting solution for preparation of the electrolyzed solution includes sodium chloride present at a concentration ranging from about 0.3 g/L to about 14 g/L, potassium chloride present at a concentration ranging from about 0.02 g/L to about 0.8 g/L, and magnesium chloride present at a concentration ranging from about 0.01 g/L to about 0.5 g/L, prior to electrolysis.
The electrolyzed acidic solutions contain, among other components, hydroxyl free radicals, oxygen, ozone, hypochlorous acid, hydrochloric acid, and hydrogen peroxide. These are the same oxidizing agents involved in physiological systems associated with wound healing and tissue repair and regeneration. For example, hypochlorous acid is the chief bactericidal agent produced by neutrophils at sites of inflammation, injury, and wounds. An adequate supply of oxygen is particularly important in collagen synthesis. In vitro studies have shown that the rate at which fibroblasts synthesize collagen is proportional to the extracellular oxygen concentration. In addition, increased crosslinking of collagen fibers, which is responsible for the increase in tensile strength of collagen, is observed in healing skin wounds with increases in the concentration of available oxygen. In vivo studies have also shown that granulation tissues in healing leg ulcers exposed to excess oxygen are characterized by abundant fibroblast proliferation.
The solutions of the invention are physiologically balanced and, when applied to infected wounds, enhance the process of healing substantially. Antimicrobial properties of acidic water solutions have been tested against many organisms, including Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Lactobacillus, yeast, vancomycin-resistant enterococcus, molds, and spores. Vancomycin-resistant bacteria, MRSA, and others are easily destroyed by the solutions of the present invention. The solutions of the invention are osmotically balanced, environmentally friendly, and have minimal cytotoxicity. For example, no cytotoxicity was observed in rabbits"" eyes nor in in vitro cytotoxicity studies carried out to date.
The composition of the invention is nontoxic and has antibacterial properties. The composition is useful in any application in which antimicrobial properties are desirable. Such applications include, without limitation, treatment of wounds, burns, and canker sores; irrigation; cleaning of tissue sites (e.g., pre- and post-operative); ophthalmic applications (e.g., in contact lens cleaning solutions or for irrigation of the eye during ophthalmic surgery); for dermatological applications, psoriasis; and numerous applications which are readily apparent to one skilled in the art. Unlike many other solutions used in similar applications, the composition of the invention has minimal to no side effects. For example, in Draize testing in Rabbit eyes, when compared to other antiseptic solutions, the physiologically balanced, electrolyzed, acidic solution of the present invention behaves in a manner similar to saline solution. he composition of the invention can be incorporated into a bandage or wound dressing, as described subsequently herein. The physiologically balanced, electrolyzed, acidic solution may be used in combination with a specially designed bandage in a wound treatment protocol as described subsequently herein. The specialized bandage includes an opening or xe2x80x9cwindowxe2x80x9d through which topical treatment materials such as the solution of the present invention may be applied.
Also disclosed herein is an article of manufacture comprising the composition of the invention packaged in a container. Surfaces of the container which are in contact with the composition of the invention are made of material which is not reactive with an oxidizing agent.